Malaria sickens over 100 million people each year. The vast majority of the victims live in endemic, tropical countries. Aggressive mosquito eradication programs in the 1940s essentially ended the incidence of locally-acquired malaria in the US, but resurgence remains a risk, so surveillance and research remain vital to US public health interests, as well as to global health interests. In the past decade, new, highly-effective antimalarial therapies have been developed based on the Chinese medicine component Qinghaosu (artemisinin) - extracted from sweet wormword (Artemisia annua). The WHO-approved treatment takes the form of a so-called artemisinin combination therapy (ACT) in which an artemisinin derivative, most commonly artemether, is combined with a longer half-life antimalarial such as lumefantrine to eliminate the parasites and decrease the risk of them developing drug resistance. The main problem is cost. Malaria victims are usually among the poorest members of the global community, and artemether is not inexpensive to make by current methods. Fortunately, Aerophase has developed a streamlined extraction/reaction/separation scheme that is anticipated to reduce the overall cost of artemether production. The first step, supercritical carbon dioxide extraction of Artemisia annua leaves, is known to isolate artemisinin and artemisinic acid in high yield. The second step, chemical conversion of these compounds to artemether, is likewise well-established. The third step, supercritical fluid extraction of the artemether product, has not been reported before, but is anticipated to work very well based on the highly lipophilic nature of artemether. Further, we anticipate that combining these steps will save on capital equipment and energy costs. The primary purpose of the proposed work is to develop a process that reduces the cost of artemether-based antimalarial products. The core technology will also be commercialized for other applications. The specific aims in phase I are 1) determine reaction conditions for conversion of artemisinin to artemether under supercritical carbon dioxide, 2) determine supercritical carbon dioxide conditions for isolation of artemether product, and 3) demonstrate that we can design and fabricate an advanced prototype that combines the extraction, reaction, and separation steps. The overall goal of this multi-phase SBIR project is to develop, validate, and commercialize a new, more cost-effective method for artemether production that utilizes supercritical carbon dioxide in an economical process. [unreadable] [unreadable] Malaria continues to be a worldwide public health problem, sickening over 100 million people per year and killing over 1 million of them. Unfortunately, malaria usually strikes populations that are least able to afford medicines. This project seeks to develop, validate, and commercialize a new, cheaper method for producing the highly effective malaria drug artemether from the Sweet Wormwood plant. [unreadable] [unreadable] [unreadable]